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Association details:
| Biomarker: | RAS mutation |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | Venclexta (venetoclax) (Bcl2 inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Venetoclax to Improve Outcomes of Fractionated Busulfan Regimen in Patients With High-Risk AML and MDS
Excerpt:
...Mutated P53 or Ras pathway genes (CBL, NRAS, KRAS, NF1, PTPN1) or DNMT 3a or ASXL1 or RUNX1 3....
Trial ID:
Source:
Title:
Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN
Excerpt:
...- Prescence of mutation in the RAS pathway including NRAS, KRAS, PTPN11, CBL, NF1, RIT1, FLT3, and KIT...
Trial ID:
Less C2 evidence
Source:
Title:
60 Overcoming Venetoclax (Ven) Resistance through Glutamine (Gln) Depletion: Final Analysis of the Phase 1 Trial of Ven and Pegcrisantaspase (PegC) Combination in Relapsed and Refractory (R/R) Acute Myeloid Leukemia (AML)
Published date:
11/02/2023
Excerpt:
ORR in Ven-refractory pts was 42% (5/12); of the 5 pts who harbored a RAS or PTPN11 mutation and previously treated with Ven, 60% responded….VenPegC is a novel regimen that can induce complete remission in some heavily pretreated R/R AML patients, even with previous exposure to Ven.
Secondary therapy:
PEGylated recombinant Erwinia chrysantemi-derived L-asparaginase
Source:
Title:
Influence of Molecular Abnormalities on Treatment Response of Venetoclax Plus Azacytidine and Homoharringtonine Versus Venetoclax Plus Hypomethylating Agent in Relapsed/Refractory Acute Myeloid Leukemia
Published date:
11/03/2022
Excerpt:
Patients with TET2 (P=0.041), NPM1 (P=0.039), ASXL1 (P=0.044), FLT3-ITD/TKD (P=0.008), DNMT3A (P<0.001) or RAS (P=0.006) mutation or co-mutation of DNMT3A and FLT3 (P=0.020, DNMT3A and NPM1 (P=0.020) or DNMT3A and IDH/2 (P=0.016) acquired statistically higher rate of CR/CRi with VAH therapy as compared with VEN+HMA trerapy....AML1-ETO-positive AML patients poorly responded to VEN+HMA therapy (0/7), but responded much better to VAH treatment (5/7, P=0.005).
Secondary therapy:
azacitidine + BS-HH-002.SA
DOI:
10.1182/blood-2022-168004
Source:
Title:
Safety and Efficacy: Clinical Experience of Venetoclax in Combination With Hypomethylating Agents in Both Newly Diagnosed and Relapsed/Refractory Advanced Myeloid Malignancies
Published date:
03/09/2021
Excerpt:
CONTRADICTED EVIDENCE: Of 26 newly diagnosed AML patients, the CR/CRi rate was 53.8%. The median DOR and OS were 6.9 months and not reached, respectively. Of 39 R/R AML patients, the CR/CRi rate was 38.5%. The median DOR and OS were both 8.1 months. Responders to HMA and venetoclax were enriched for TET2, IDH1, and IDH2 mutations, while nonresponders were associated with FLT3 and RAS mutations.
DOI:
10.1097/HS9.0000000000000549
Source:
Title:
Molecular Patterns of Response and Outcome in the Chemotherapy and Venetoclax in Elderly AML Trial (CAVEAT study)
Published date:
11/01/2018
Excerpt:
Responses in response-evaluable patients were most common in NPM1 mutant AML (100%; n=7), followed by RUNX1 (90%; n=11), RAS (90%; n=10) and IDH (89%; n=9)...To date, VEN up to 600mg in combination with 5+2 induction chemotherapy is tolerable in fit elderly patients with AML. Initial response rates >80% were observed in de novo AML, as well as NPM1, RUNX1, RAS and IDH mutant AML…
Secondary therapy:
cytarabine + idarubicin
DOI:
doi.org/10.1182/blood-2018-99-114243
